(Animation of an IgE-Mediated Allergic Reaction to Food)
IgE-Mediated Food Allergies
Arguably, IgE-mediated food allergies are the most important class of food sensitivities for several reasons. First, although the number of affected individuals is relatively small, the reactions in some individuals in this group can be quite severe and even life-threatening especially if a significant quantity of the offending food is inadvertently ingested. Also, the degree of tolerance for the offending food is small (very small in some individuals) making the implementation of safe and effective avoidance diets more difficult.
IgE-mediated food allergies are true food allergies involving an abnormal response of the immune system to one or more specific foods. These are immediate hypersensitivity reactions.
IgE-mediated reactions are associated with the rapid onset of symptoms - usually within a few minutes to a few hours after the ingestion of the offending food. Immediate hypersensitivity reactions are mediated by an allergen-specific immunoglobulin E (IgE) antibody as depicted in Figure 1. The food allergens involved in IgE-mediate reactions are typically naturally-occurring proteins in foods (put link to section on food allergens). In IgE-mediated food allergies, exposure to the allergen stimulates the production of allergen-specific IgE antibodies by plasma cells in susceptible individuals. The allergen-specific IgE attaches itself to the surface of mast cells in various tissues and basophils in the blood in a process known as sensitization. No symptoms occur during the sensitization phase but, once that phase is completed, the individual is primed to react to the offending allergen.
During the sensitization phase, the susceptible individual will form allergen-specific IgE antibodies upon exposure to a specific food protein. However, even among susceptible individuals, exposure to food proteins does not usually result in the formation of IgE antibodies. In normal individuals, exposure to a food protein in the gastrointestinal tract results in oral tolerance through either the formation of protein-specific IgG, IgM, or IgA antibodies or no immunological response whatsoever (clonal anergy). Thus, oral tolerance is the "normal" homeostatic state in humans. IgE-mediated food allergy can be viewed as a breakdown in oral tolerance. But, those consumers who develop IgE-mediated food allergies are still likely to be tolerant to the vast majority of foods in their diets. Many are allergic to only one or several related foods, although some may be allergic to multiple foods (very rarely more than 5 foods).
Why do some individuals develop IgE-mediated food allergy while most consumers develop oral tolerance to foods? Heredity and other physiological factors are important in predisposing individuals to the development of IgE-mediated allergies including food allergies. Studies with monozygotic and dizygotic twins demonstrate that genetics is an extremely important factor because such relatedness enhances the likelihood of developing an allergy. Identical twins may even inherit the likelihood of responding to the same allergenic food, e.g. peanuts (see Sicherer SH, Furlong TJ, Maes HH, et al. Journal of Allergy & Clinical Immunology 2000; 106:53-6). Approximately 65% of patients with clinically documented allergy have first degree relatives with allergic disease, although not necessarily food allergy. Conditions that increase the permeability of the small intestinal mucosa to proteins such as viral gastroenteritis, premature birth, and cystic fibrosis also seem to increase the risk of development of food allergy.
Sensitization to foods is most likely to occur in infancy or early childhood but sensitization can and does occur in susceptible individuals throughout life. Sensitization is more likely to occur to foods eaten early in life and to foods that are good sources of protein that are consumed in comparatively large amounts. Hence, milk and eggs are important allergenic foods for infants and young children. Sensitization may not occur on the first exposure to the offending food. Thus, oral tolerance may be established and later break down for reasons that are not fully understood. For example, we once encountered an individual with severe soybean allergy who did not experience her first allergic reaction to soybeans until she was over 50 years of age. Clearly, she must have been exposed to soybeans on multiple occasions before developing an allergic sensitization to soybean but it was never clear what might have provoked the breakdown of oral tolerance in this case.
While no symptoms occur during the sensitization phase, this process does prime the affected individual for the onset of an allergic reaction to a specific food. Upon subsequent exposure to the allergenic food, the allergen cross-links IgE molecules on the surface of the mast cell or basophil membrane causing these cells to release various mediators of the allergic reaction into the bloodstream and tissues. Several dozen physiologically active mediators of the allergic reaction have been identified. Histamine is one of the most important mediators of the immediate hypersensitivity reaction. Histamine alone can elicit inflammation, pruritis (itching), and contraction of the smooth muscles in the blood vessels, gastrointestinal tract, and respiratory tract. Other important mediators include various leukotrienes and prostaglandins. The released mediators interact with receptors in various tissues eliciting a wide range of physiologic responses. Because the mediators are released into the bloodstream, systemic reactions involving multiple tissues and organs can ensue.
Other allergies also occur through this same IgE-mediated mechanism including allergies to pollens, mold spores, animal danders, dust mites, certain drugs (e.g. penicillin), and bee venom. Susceptible individuals may form allergen-specific IgE to one or several substances in their environment including food allergens. Occupational food allergies are also known to occur where individuals are affected by contact with or inhalation of the offending food rather than by its ingestion.